Soluble form of the receptor for advanced glycation end-products attenuates inflammatory pathogenesis in a rat model of lipopolysaccharide-induced lung injury

Yasuhisa Izushi, Kiyoshi Teshigawara, Keyue Liu, Dengli Wang, Hidenori Wake, Katsuyoshi Takata, Tadashi Yoshino, Hideo Kohka Takahashi, Shuji Mori, Masahiro Nishibori

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Abstract

Acute respiratory distress syndrome (ARDS) is a severe respiratory failure caused by acute lung inflammation. Recently, the receptor for advanced glycation end-products (RAGE) has attracted attention in the lung inflammatory response. However, the function of soluble form of RAGE (sRAGE), which is composed of an extracellular domain of RAGE, in ARDS remains elusive. Therefore, we investigated the dynamics of pulmonary sRAGE and the effects of exogenous recombinant human sRAGE (rsRAGE) under intratracheal lipopolysaccharide (LPS)-induced lung inflammation. Our result revealed that RAGE was highly expressed on the alveolar type I epithelial cells in the healthy rat lung including sRAGE isoform sized 45 kDa. Under LPS-induced injured lung, the release of sRAGE into the alveolar space was increased, whereas the expression of RAGE was decreased with alveolar disruption. Treatment of the injured lung with rsRAGE significantly suppressed the lung edema, the neutrophils infiltration, the release of high mobility group box-1 (HMGB1), and the expressions of TNF-α, IL-1β and iNOS. These results suggest that the alveolar release of sRAGE may play a protective role against HMGB1 as well as exogenous pathogen-associated molecular patterns. Supplementary therapy with sRAGE may be an effective therapeutic strategy for ARDS.

Original languageEnglish
JournalJournal of Pharmacological Sciences
DOIs
Publication statusAccepted/In press - Dec 23 2015

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Lung Injury
Lipopolysaccharides
Lung
Adult Respiratory Distress Syndrome
Pneumonia
Alveolar Epithelial Cells
Neutrophil Infiltration
Interleukin-1
Respiratory Insufficiency
Advanced Glycosylation End Product-Specific Receptor
Edema
Protein Isoforms
Therapeutics

Keywords

  • AECI
  • Anti-inflammation
  • ARDS
  • LPS
  • RAGE

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine

Cite this

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title = "Soluble form of the receptor for advanced glycation end-products attenuates inflammatory pathogenesis in a rat model of lipopolysaccharide-induced lung injury",
abstract = "Acute respiratory distress syndrome (ARDS) is a severe respiratory failure caused by acute lung inflammation. Recently, the receptor for advanced glycation end-products (RAGE) has attracted attention in the lung inflammatory response. However, the function of soluble form of RAGE (sRAGE), which is composed of an extracellular domain of RAGE, in ARDS remains elusive. Therefore, we investigated the dynamics of pulmonary sRAGE and the effects of exogenous recombinant human sRAGE (rsRAGE) under intratracheal lipopolysaccharide (LPS)-induced lung inflammation. Our result revealed that RAGE was highly expressed on the alveolar type I epithelial cells in the healthy rat lung including sRAGE isoform sized 45 kDa. Under LPS-induced injured lung, the release of sRAGE into the alveolar space was increased, whereas the expression of RAGE was decreased with alveolar disruption. Treatment of the injured lung with rsRAGE significantly suppressed the lung edema, the neutrophils infiltration, the release of high mobility group box-1 (HMGB1), and the expressions of TNF-α, IL-1β and iNOS. These results suggest that the alveolar release of sRAGE may play a protective role against HMGB1 as well as exogenous pathogen-associated molecular patterns. Supplementary therapy with sRAGE may be an effective therapeutic strategy for ARDS.",
keywords = "AECI, Anti-inflammation, ARDS, LPS, RAGE",
author = "Yasuhisa Izushi and Kiyoshi Teshigawara and Keyue Liu and Dengli Wang and Hidenori Wake and Katsuyoshi Takata and Tadashi Yoshino and Takahashi, {Hideo Kohka} and Shuji Mori and Masahiro Nishibori",
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T1 - Soluble form of the receptor for advanced glycation end-products attenuates inflammatory pathogenesis in a rat model of lipopolysaccharide-induced lung injury

AU - Izushi, Yasuhisa

AU - Teshigawara, Kiyoshi

AU - Liu, Keyue

AU - Wang, Dengli

AU - Wake, Hidenori

AU - Takata, Katsuyoshi

AU - Yoshino, Tadashi

AU - Takahashi, Hideo Kohka

AU - Mori, Shuji

AU - Nishibori, Masahiro

PY - 2015/12/23

Y1 - 2015/12/23

N2 - Acute respiratory distress syndrome (ARDS) is a severe respiratory failure caused by acute lung inflammation. Recently, the receptor for advanced glycation end-products (RAGE) has attracted attention in the lung inflammatory response. However, the function of soluble form of RAGE (sRAGE), which is composed of an extracellular domain of RAGE, in ARDS remains elusive. Therefore, we investigated the dynamics of pulmonary sRAGE and the effects of exogenous recombinant human sRAGE (rsRAGE) under intratracheal lipopolysaccharide (LPS)-induced lung inflammation. Our result revealed that RAGE was highly expressed on the alveolar type I epithelial cells in the healthy rat lung including sRAGE isoform sized 45 kDa. Under LPS-induced injured lung, the release of sRAGE into the alveolar space was increased, whereas the expression of RAGE was decreased with alveolar disruption. Treatment of the injured lung with rsRAGE significantly suppressed the lung edema, the neutrophils infiltration, the release of high mobility group box-1 (HMGB1), and the expressions of TNF-α, IL-1β and iNOS. These results suggest that the alveolar release of sRAGE may play a protective role against HMGB1 as well as exogenous pathogen-associated molecular patterns. Supplementary therapy with sRAGE may be an effective therapeutic strategy for ARDS.

AB - Acute respiratory distress syndrome (ARDS) is a severe respiratory failure caused by acute lung inflammation. Recently, the receptor for advanced glycation end-products (RAGE) has attracted attention in the lung inflammatory response. However, the function of soluble form of RAGE (sRAGE), which is composed of an extracellular domain of RAGE, in ARDS remains elusive. Therefore, we investigated the dynamics of pulmonary sRAGE and the effects of exogenous recombinant human sRAGE (rsRAGE) under intratracheal lipopolysaccharide (LPS)-induced lung inflammation. Our result revealed that RAGE was highly expressed on the alveolar type I epithelial cells in the healthy rat lung including sRAGE isoform sized 45 kDa. Under LPS-induced injured lung, the release of sRAGE into the alveolar space was increased, whereas the expression of RAGE was decreased with alveolar disruption. Treatment of the injured lung with rsRAGE significantly suppressed the lung edema, the neutrophils infiltration, the release of high mobility group box-1 (HMGB1), and the expressions of TNF-α, IL-1β and iNOS. These results suggest that the alveolar release of sRAGE may play a protective role against HMGB1 as well as exogenous pathogen-associated molecular patterns. Supplementary therapy with sRAGE may be an effective therapeutic strategy for ARDS.

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